Phosphoproteomics in drug discovery

• Phosphoproteomic technologies deliver highly informative data to aide drug discovery.
• Technologies include mass spectrometry and suspension and planar protein arrays.
• Technologies have distinct advantages and limitations and are highly complementary.
• Phosphoproteomics informs on the biology and chemistry of a drug.
• Applications include target ID, biomarker ID, MOA, toxicity, pathways and repositioning.

Several important aspects of the drug discovery process, including target identification, mechanism of action determination and biomarker identification as well as drug repositioning, require complete understanding of the effects of drugs on protein phosphorylation in relevant biological systems. Novel high-throughput phosphoproteomic technologies can be employed to measure these phosphorylation events. In this review, we describe the advantages and limitations of state-of-the-art phosphoproteomic approaches such as mass spectrometry and antibody-based technologies in terms of sample and data throughput as well as data quality. We then discuss how datasets from each technology can be analyzed and how the results can be and have been applied to advance different aspects of the drug discovery process.